Sex Differences in Binge-Like Alcohol Consumption in Mice: Involvement of Beta-endorphin and the Stress Axis

Binge drinking is a widespread problem in the Unites States and has been linked to an increased risk for alcohol-related complications including the development of alcohol use disorders (King, de Wit, McNamara, & Cao, 2011). Therefore, understanding the underlying mechanisms of binge drinking may facilitate identification of therapeutic targets to prevent the transition toward alcoholism. Beta-endorphin (B-E) is an endogenous opioid peptide thought to contribute to the risk for disordered drinking. Low basal plasma levels and an increased B-E response to alcohol consumption are evident in at-risk human populations (Gianoulakis, Krishnan, & Thavundayil, 1996) as well as alcohol- preferring rodents (De Waele & Gianoulakis, 1994). Here, we tested whether B- E is necessary for binge alcohol consumption using a modified drinking in the dark (DID) model (Rhodes, Best, Belknap, Finn, & Crabbe, 2005). Adult male and female C57BL/6J controls (B6) and B-E deficient (KO) mice were provided with a 2 bottle choice of either 20% ethanol (EtOH) or water, or water in both bottles, starting 3 hours into their dark cycle for 4 consecutive days (Giardino & Ryabinin, 2013). Following the binge test on day 4, mice were rapidly decapitated for collection of trunk blood to assess blood alcohol concentration and plasma corticosterone (CORT). Brains were dissected and frozen for mRNA analysis of corticotropin releasing hormone (CRH) in several limbic structures using qRT-PCR. We find sex-specific effects of B-E on binge EtOH consumption. B-E deficient females consume more ethanol than B-E deficient males. Overall, B-E deficient mice have higher basal CORT than B6 counterparts, and this genetic difference was affected by ethanol differently in male and female mice. In B-E deficient females binge-like ethanol consumption reduced CORT to levels similar to female B6 mice, but B-E deficient males were unaffected by alcohol consumption. These results suggest that B-E has sexually dimorphic effects on binge-like EtOH consumption, perhaps reflecting a heightened propensity to drink to alleviate a stress phenotype in B-E deficient females